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Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy.

Abstract
Measurements of early tumor responses to therapy have been shown, in some cases, to predict treatment outcome. We show in lymphoma-bearing mice injected intravenously with hyperpolarized [1-(13)C]pyruvate that the lactate dehydrogenase-catalyzed flux of (13)C label between the carboxyl groups of pyruvate and lactate in the tumor can be measured using (13)C magnetic resonance spectroscopy and spectroscopic imaging, and that this flux is inhibited within 24 h of chemotherapy. The reduction in the measured flux after drug treatment and the induction of tumor cell death can be explained by loss of the coenzyme NAD(H) and decreases in concentrations of lactate and enzyme in the tumors. The technique could provide a new way to assess tumor responses to treatment in the clinic.
AuthorsSam E Day, Mikko I Kettunen, Ferdia A Gallagher, De-En Hu, Mathilde Lerche, Jan Wolber, Klaes Golman, Jan Henrik Ardenkjaer-Larsen, Kevin M Brindle
JournalNature medicine (Nat Med) Vol. 13 Issue 11 Pg. 1382-7 (Nov 2007) ISSN: 1078-8956 [Print] United States
PMID17965722 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Carbon Isotopes
  • Lactic Acid
  • Etoposide
  • Pyruvic Acid
  • Lactate Dehydrogenases
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (administration & dosage)
  • Carbon Isotopes (metabolism)
  • Cell Death (drug effects)
  • Cell Line, Tumor
  • Etoposide (administration & dosage)
  • Lactate Dehydrogenases (metabolism)
  • Lactic Acid (administration & dosage, metabolism)
  • Lymphoma (drug therapy, enzymology, pathology)
  • Magnetic Resonance Imaging (methods)
  • Magnetic Resonance Spectroscopy (methods)
  • Mice
  • Neoplasm Transplantation
  • Pyruvic Acid (administration & dosage, metabolism)

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